Brain stimulation systems and methods

ABSTRACT

Systems and methods for brain stimulation.

The present invention relates generally to brain stimulation systems andmethods. More specifically, the present invention relates to systems andmethods that may enhance memory consolidation by stimulatingneurophysiological events during wakefulness and during sleep.

Electroencephalography (EEG) records the neural activity of electricalpotential across cell membranes, which are detected through the cerebralcortex and recorded by a plurality of electrodes. The changes inelectrical potential in the cortex contain rhythmical activity, whichtypically occur at frequencies of about 0.5 to 70 cycles per second(hertz). While awake, fast, random signals are predominantly generatedat low voltage and mixed frequency. While asleep, more predictablesignals are generated at a low voltage and predictable frequencies overpredictable periods.

Five distinct brain wave patterns that are commonly detected during anEEG recording are delta waves (e.g., about 0.5-3 hertz), theta waves(e.g., about 3-8 hertz), alpha waves (e.g., about 8-12 hertz), betawaves (e.g., about 13-38 hertz), and gamma waves (e.g., about 38-70hertz). Many of these frequencies may be observed in a subject's sleepcycle. A sleep cycle may be defined as a progression of brainwavepatterns that may be seen while a subject is sleeping. Generally,subjects undergo several sleep cycles per night, each lasting aroundninety minutes. Each progression of brainwave patterns during the sleepcycle may be referred to as a stage of the sleep cycle. Generally, eachsleep cycle progresses consecutively through stage I sleep, stage IIsleep, stage III sleep, stage IV sleep (stage III sleep and stage IVsleep may be grouped together and referred to as slow wave sleep),briefly back to stage II sleep, and then rapid eye movement (REM) sleep.

During stage I sleep, a subject's brain waves slow in frequencytransitioning from alpha waves to theta waves. During stage II sleep, asubject's brain waves slow further and include various bursts ofactivity such as sleep spindles and K-complexes. Sleep spindles, as seenon an EEG recording, are brain wave patterns that begin low in amplitudeand gradually increase amplitude before gradually decreasing over asecond or two. Sleep spindles may also be referred to as acrescendo-decrescendo pattern. In general, sleep spindles have afrequency of about 12-14 hertz. K-complexes are brain wave patterns thatinclude large, relatively-slow waves (e.g., 1-2 hertz) and may occurduring stage II sleep. During stage III sleep, a subject's brain wavesslow further in frequency and may be defined by a period in which deltawaves are less than 50 percent of the total wave patterns. During stageIV sleep, a subject's brain waves slow further still and may be definedby period in which delta waves make up between 20 and 50 percent of thewave patterns. During REM sleep, a subject's brain waves increase infrequency to the gamma frequency similar to the brain waves observedduring waking consciousness.

Further, during REM sleep, various bursts of sawtooth waves may beobserved. The sawtooth waves that may be seen during REM sleep mayprecede a burst of rapid eye movements. Sawtooth waves, as seen on anEEG recording, look like a series of shark fins that oscillate at thetheta frequency. Although REM sleep is characterized by actual rapid eyemovement, periods of little to no eye movements may occur during REMsleep (tonic REM), which are then punctuated by bursts of rapid eyemovement (phasic REM).

Waking consciousness is generally experienced neurophysiologically at abrainwave frequency of about forty hertz. The amygdala is part of thelimbic system that judges emotional relevance of an experience. When theamygdala and/or the rest of the limbic system experience an event thathas enough emotional relevance, the event is temporarily stored in thehippocampus. A subject's brain hippocampal wave frequency is generallyabout 3-8 hertz (the theta frequency) when such events are temporarilystored in the hippocampus.

Electrooculography (EOG) records the ocular activity of the electricalpotential from the retina, which consists of an electrically-chargednerve membrane. EOG signals can be measured by placing electrodes nearan eye. Motion of an eye may cause a measurable change of electricalpotential between two or more surface electrodes.

Electromyography (EMG) records the muscular activity of electricalpotential across muscular membranes, which range between about 50microvolts to about 300 millivolts (depending on the muscle underobservation). Typical repetition rate of muscle unit firing is about 7hertz to about 200 hertz, depending on the size of the muscle, the typeof muscle, etc. EMG signals may be recorded within a muscle (i.e.,intramuscular EMG) or on the surface a subject's skin outside of amuscle.

A subject's EOG and/or EMG may also be useful in determining the sleepcycle of a subject. For example, when phasic burst of EOG eye movementsare seen during low EMG activity along with simultaneous low voltage,mixed frequency EEG activity, the subject is likely to be in REM sleep.

Physical tasks (e.g., trampolining), learning tasks (e.g., learning aforeign language or learning Morse code), and visual tasks (e.g., visualfield inversion or visual discrimination tasks) have been shown todemonstrate increases in REM sleep following successful learning. Brainwave recordings in animals have shown that the same brain areas that areactivated during learning while awake are again activated during thatnight's REM sleep. For example, the brain wave frequency recorded in thehippocampus of rats while learning “wheel running” is in the thetafrequency. The same brainwave pattern and frequency, i.e., the thetafrequency, may be seen the hippocampus of the same rats duringsubsequent slow wave sleep and then during subsequent REM sleep.Further, this correlation has also been witnessed in rats performingother learning behavior, such as running wheels and mazes, and in otheranimals, such as zebra finches as they are learning and rehearsingsongs.

Transcranial electric stimulation (TES) may deliver electrical currentstimulation to the brain. When TES is used through the scalp tostimulate the frontal lobes during slow wave sleep over thirty minuteperiods, memory word pairs learning during wakefulness may be improved.It was concluded that the effects of transcranial direct corticalstimulation enhanced the generation of slow waves and thus facilitatedthe processes of neuronal plasticity.

Performance of a simple finger-tapping task was, in one study, improvedby about twenty percent if the subjects were allowed a night of sleepbetween training and retesting. Further, high correlation existedbetween post-sleep performance and the amount of stage II sleep obtainedin the last quarter of the sleep night.

Subjects tested on a series of procedural motor tasks, e.g., a pursuitrotor task, a motor task involving dexterity with a ball and cup, adirect trace task, and the fine manual dexterity game “Operation,” havebeen shown to have an increase in the total number of stage II sleepspindles. Subjects that were not exposed to the tasks showed no changein the number of sleep spindles.

Clicking noises delivered to subjects at the same time as the subjectsundergo the sleep spindles of stage II sleep and as the subjects ascendfrom slow wave sleep towards REM sleep have been shown to increasecentral nervous system excitability.

Transcranial magnetic stimulation (TMS) refers to a noninvasiveexcitation of neurons in the brain by utilizing magnetic fields toinduce electric currents the brain. An example of TMS may involveplacing a treatment coil that generates a magnetic field near asubject's head. The magnetic field may induce an electrical current inthe brain causing neurons to fire, which may induce various chemicalchanges in the brain.

SUMMARY OF THE INVENTION

In one aspect, the present invention provides a method of stimulating asubject's brain. The method may include providing stimulation apparatus(e.g., TMS apparatus, auditory stimulation apparatus, visual stimulationapparatus, olfactory stimulation apparatus, somatosensory stimulationapparatus, etc.) for delivering stimulation to a subject and monitoringapparatus (e.g., EEG apparatus, EOG apparatus, EMG apparatus, etc.) tomeasure the state of the subject, e.g., through the activity of thesubject's brain. The method may further include positioning thestimulation apparatus where the subject can receive the stimulation,delivering stimulation from the stimulation apparatus to the subjectduring one or more first periods when the subject is awake, anddelivering stimulation from the stimulation apparatus to the subjectduring one or more second periods when the subject is asleep.

In another aspect, the present invention provides a stimulation systemfor stimulating a subject. The system may include a learning componentand a consolidation component. The learning component may includeauditory stimulation apparatus for delivering one or more selectedauditory stimulations to the subject and one or more self-actuationinputs operably coupled to the auditory stimulation apparatus forself-actuation by the subject to deliver at least one selected auditorystimulation of the one or more selected auditory stimulations to thesubject. The consolidation component may include monitoring apparatusfor monitoring the sleep state of a subject, wherein the monitoringapparatus comprises one or more electrodes, auditory stimulationapparatus for delivering one or more selected auditory stimulations tothe subject, and a controller electrically coupled to the monitoringapparatus to receive input regarding the sleep state of the subject fromthe monitoring apparatus and the auditory stimulation apparatus tooperate the auditory stimulation apparatus. The controller may utilizethe input from the monitoring apparatus to determine when the subject isin one or more selected sleep states. Further, the controller mayoperate the auditory stimulation apparatus to deliver at least oneselected auditory stimulation of the one or more selected auditorystimulations previously delivered by the learning component to thesubject during at least one selected sleep state of the one or moreselected sleep states.

In another aspect, the present invention provides a method ofstimulating a subject's brain. The method may include providingstimulation apparatus for delivering stimulation to a subject andelectroencephalography apparatus to measure the electrical activity ofthe subject's brain. The method may further include positioning thestimulation apparatus where the subject can receive the stimulation,delivering stimulation from the stimulation apparatus to the subjectduring one or more first periods when the subject is awake, anddelivering stimulation from the stimulation apparatus to the subjectduring one or more second periods when the subject is asleep.

In another aspect, the present invention provides a method ofstimulating a subject's brain. The method may include providingstimulation apparatus for delivering transcranial magnetic stimulationand electroencephalography apparatus to measure the electrical activityof the subject's brain. The method may further include positioning thestimulation apparatus proximate the subject's brain, wherein thestimulation apparatus is located external to the subject's skull,delivering transcranial magnetic stimulation from the stimulationapparatus to the subject's brain during a first period when the subjectis awake, and delivering transcranial magnetic stimulation from thestimulation apparatus to the subject's brain during a second period whenthe subject is asleep.

In another aspect, the present invention provides a method ofstimulating a subject's brain. The method may include providing auditorystimulation apparatus for delivering auditory stimulation to a subjectand electroencephalography apparatus to measure the electrical activityof the subject's brain. The method may further include positioning theauditory stimulation apparatus where the subject can hear the auditorystimulation, delivering auditory stimulation from the auditorystimulation apparatus to the subject during one or more first periodswhen the subject is awake, and delivering auditory stimulation from theauditory stimulation apparatus to the subject during one or more secondperiods when the subject is asleep.

In another aspect, the present invention provides a stimulation system.The stimulation system may include electroencephalography apparatus,stimulation apparatus, and a controller electrically coupled to theelectroencephalography apparatus and the stimulation apparatus. Theelectroencephalography apparatus may includes one or more electrodes.The controller may receive input from the electroencephalographyapparatus, and the controller may control the stimulation apparatus.

In another aspect, the present invention provides a stimulation system.The stimulation system may include electroencephalography apparatus,transcranial magnetic stimulation apparatus, and a controllerelectrically coupled to the electroencephalography apparatus and thetranscranial magnetic stimulation apparatus. The electroencephalographyapparatus may include one or more electrodes. The transcranial magneticstimulation apparatus may include one or more treatment coils. Thecontroller may receive input from the electroencephalography apparatus,and the controller may control the transcranial magnetic stimulationapparatus.

In another aspect, the present invention provides a stimulation system.The stimulation system may include electroencephalography apparatus,auditory stimulation apparatus, and a controller electrically coupled tothe electroencephalography apparatus and the auditory stimulationapparatus. The electroencephalography apparatus may include one or moreelectrodes. The controller may receive input from theelectroencephalography apparatus, and the controller may control theauditory stimulation apparatus.

In still another aspect, the present invention provides a stimulationsystem. The stimulation system may include monitoring apparatus formonitoring the sleep state of a subject, auditory stimulation apparatusfor delivering one or more selected auditory stimulations to the subjectone or more self-actuation inputs for self-actuation by the subject todeliver at least one selected auditory stimulation of the one or moreselected auditory stimulations to the subject, and a controllerelectrically coupled to the monitoring apparatus, the auditorystimulation apparatus, and the one or more self-actuation inputs. Themonitoring apparatus may include one or more electrodes. Further, thecontroller may receive input from the monitoring apparatus to determineif the subject is in one or more the selected sleep states. Stillfurther, the controller may operate the auditory stimulation apparatusto deliver at least one of the one or more selected auditorystimulations to the subject when the subject is determined to be in oneor more of the selected sleep states.

In yet still another aspect, the present invention provides a method ofstimulating a subject's brain. The method may include providing auditorystimulation apparatus for delivering one or more auditory stimulationsto a subject and providing monitoring apparatus to monitor the state ofthe subject. Further, the method may include positioning the auditorystimulation apparatus where the subject can hear the auditorystimulation and delivering at least one auditory stimulation of the oneor more auditory stimulations from the auditory stimulation apparatus tothe subject during one or more first periods when the subject is awake.Still further, the method may include delivering the at least oneauditory stimulation of the one or more auditory stimulations from theauditory stimulation apparatus to the subject during one or more secondperiods when the subject is asleep.

The above summary is not intended to describe each embodiment or everyimplementation of the present invention. Rather, a more completeunderstanding of the invention will become apparent and appreciated byreference to the following Detailed Description of Exemplary Embodimentsand claims in view of the accompanying figures of the drawing.

BRIEF DESCRIPTION OF THE DRAWING

FIG. 1 is a flow chart of one exemplary method of stimulating asubject's brain according to the present invention.

FIG. 2 is a flow chart of another exemplary method stimulating subject'sbrain according to the present invention.

FIG. 3 is a flow chart of another exemplary method stimulating subject'sbrain according to the present invention.

FIG. 4 is a flow chart of another exemplary method stimulating subject'sbrain according to the present invention.

FIG. 5A is a flow chart of another exemplary method stimulatingsubject's brain according to the present invention.

FIG. 5B is a flow chart of still another exemplary method stimulatingsubject's brain according to the present invention.

FIG. 6 is a diagrammatic representation of one exemplary transcranialmagnetic stimulation system according to the present invention.

FIG. 7 is a diagrammatic representation of one exemplary auditory and/orvisual stimulation system according to the present invention.

FIG. 8 is an illustrative view of one exemplary embodiment of thetranscranial magnetic stimulation system according to the presentinvention.

FIG. 9A is an illustrative view of one exemplary embodiment of anauditory stimulation system according to the present invention.

FIG. 9B is an illustrative view of one exemplary embodiment of anauditory/visual stimulation system according to the present invention.

FIG. 9C is an illustrative view of another exemplary embodiment of anauditory/visual stimulation system according to the present invention.

FIG. 10 is a diagrammatic representation of one exemplary stimulationsystem according to the present invention.

FIG. 11 is an illustrative view of the stimulation system of FIG. 9B.

FIG. 12 is an illustrative view of one exemplary embodiment of astimulation system according to the present invention.

FIG. 13 is a diagrammatic representation of one exemplary configurationapparatus according to the present invention.

FIG. 14 is a diagrammatic representation of a configuration of astimulation system according to the present invention.

FIG. 15 is a diagrammatic representation of one exemplary embodiment ofa stimulation system according to the present invention.

DESCRIPTION OF EXEMPLARY EMBODIMENTS

In the following detailed description of illustrative embodiments of theinvention, reference is made to the accompanying figures of the drawingwhich form a part hereof, and in which are shown, by way ofillustration, specific embodiments in which the invention may bepracticed. It is to be understood that other embodiments may be utilizedand structural changes may be made without departing from the scope ofthe present invention.

As used herein, “a,” “an,” “the,” “at least one,” and “one or more” areused interchangeably. The term “and/or” (if used) means one or all ofthe listed elements or a combination of any two or more of the listedelements.

FIG. 1 depicts one exemplary method 100 of stimulating a subject's brainaccording to the present invention. In this method, TMS apparatus may beprovided 102. The TMS apparatus used in this method 100 may be anyapparatus capable of providing TMS to a subject. Examples of somepotentially suitable TMS apparatus may include, e.g., a NeuroStar TMSTherapy System from Neuronetics, Inc. The TMS apparatus may include apower supply, a control system, a display system, at least one treatmentcoil, and/or any other component as would be known by one of ordinaryskill in the art. The TMS apparatus may be autonomous, or may beoperated by an operator. In at least one embodiment, the subject mayself-administer the TMS. The TMS apparatus may be stationary or portable(in which case it may include a portable power supply).

Monitoring apparatus 104 may also be provided in connection with thesystems of the present invention. The monitoring apparatus may include apower supply, a control system, a display system, at least oneelectrode, and/or any other component as would be known by one ofordinary skill in the art. The monitoring apparatus may be autonomous,or may be operated by an operator. In at least one embodiment, thesubject may self-administer the monitoring apparatus. The monitoringapparatus may be stationary or portable (in which case it may include aportable power supply).

The TMS apparatus and the monitoring apparatus may be positionedproximate the subject's brain 106. As described herein, the TMSapparatus may include one or more treatment coils that may providemagnetic stimulation to, e.g., the subject's brain by producing one ormore magnetic fields. The treatment coils may be positioned proximateone or more selected portions of the subject's brain. Further, asdescribed herein, the monitoring apparatus may include one or moreelectrodes to detect electrical activity (e.g., EEG) of the subject'sbrain, muscular activity (e.g., EMG) of the subject, and/or ocularactivity (e.g., EOG) of the subject. The one or more electrodes may bepositioned proximate one or more portions of the subject's head and/orsubject's brain. In at least one embodiment according to the presentinvention, the TMS apparatus and the monitoring apparatus may beintegrated so that, e.g., the same apparatus may be positioned proximatethe subject's head and provide both the TMS and monitoring functions.

The treatment coils of the TMS apparatus may be positioned proximate thesubject's brain to stimulate one or more selected portions of thesubject's brain. For example, the treatment coils may be positioned tostimulate the various cortical and deep brain structures including thefrontal lobes, the temporal lobes, the parietal lobes, the occipitalcortex, the hippocampus, the amygdala, etc. The selected portions of thebrain stimulated by TMS may be selected to correspond to the learningtask that the method is intended to improve as understood by one ofordinary skill in neurophysiology. For example, a subject's precentralgyrus corresponding to the right hand may be stimulated with TMS in anattempt to improve the subject's coordination of a learned skillinvolving the right hand because the precentral gyrus corresponding tothe right hand is known in neurophysiology to correspond with right handmovements.

The electrodes of the monitoring apparatus may be positioned proximatethe subject's head to monitor, e.g., one or more selected portions ofthe subject's brain and/or head, etc. For example, the electrodes may bepositioned proximate the subject's eyes, forehead, frontal lobes,temporal lobes, parietal lobes, occipital lobes, the cerebral cortexoverlaying the hippocampus, amygdala, etc. The one or more selectedportions of the subject's brain and/or head to be monitored by themonitoring apparatus may be selected based on what portions of the brainmay be involved in the task at hand. Additionally, the monitoringapparatus may monitor the state of consciousness or sleep stage thesubject is in at any given moment. For example, a subject's frontal lobejust above the eye may be monitored by the monitoring apparatus becausethe stage of sleep may be determined through an analysis of brain waves(e.g., EEG), eye movements (e.g., EOG), and muscle tone (e.g., EMG).

The TMS as delivered to a subject may include magnetic fieldsoscillating at one or more selected frequency ranges, e.g., a frequencyof about 3 hertz or more, about 8 hertz or less, or faster or slowerfrequency ranges. Other variations in the delivery of TMS may includevariations in magnetic field strength. For example, the magnetic fieldstrength used in connection with the present invention as measures atthe subject's scalp may be about 1 tesla or more, about 4 teslas orless, etc. Further, other variations in the delivery of TMS may includevariations in waveform morphology and/or variations in the patterns ofwaveforms through time.

Although the method 100 depicted in FIG. 1 involves positioning both theTMS apparatus and the monitoring apparatus proximate the subject's headbefore delivering TMS to the subject's brain when the subject is awake108, other embodiments may not position the monitoring apparatusproximate the subject's head until after the TMS is delivered when thesubject is awake 108 (i.e., before TMS is delivered when the subject isasleep 110). In other words, the monitoring apparatus may not be usedwhile the subject is awake.

The TMS may be delivered to the subject when the subject is awake duringa selected time period, during one or more selected time periods, orcontinuously. The delivery of TMS to the subject's brain 110 while thesubject is awake may only occur while the subject is learning a specifictask. Such learning may include memorization, reading and comprehension,motor skills, verbal fluency, any other learning paradigm, etc. Further,the delivery of TMS to the subject's brain 110 while the subject isawake may only occur when the electrical activity in the subject's brainindicates that the subject is in a particular state. For example, asdescribed herein, one such state may be when a subject's hippocampalbrainwaves are operating in the theta frequency (or any other selectedfrequency range).

The TMS may be delivered to the subject when the subject is asleepduring a selected time period, during one or more selected time periods,or continuously. The delivery of TMS while a subject is both awake andasleep may create an association between the learning task and/or tasksthat the subject experienced during the awake period and the memoryconsolidation of such learning task or tasks while sleeping.

FIG. 2 depicts another exemplary method of stimulating a subject's brainaccording to the present invention. The steps 202, 204, 206, 208, and212 are similar to the steps 102, 104, 106, 108, and 110, respectively,described herein with respect to FIG. 1. The method 200 depicted in FIG.2 includes determining if the subject's brain is in a selected statebefore delivering TMS to the subject's brain. This selective delivery ofTMS may be performed during selected sleep stages and/or selectedportions of stages of the subject's sleep cycle as described herein.

The determination step 210 of method 200 may, for example, includedetermining if the subject is experiencing actual rapid eye movement(e.g., using the monitoring apparatus), and if so, delivering a periodof TMS 212. After the delivery of TMS 212, the method 200 may loop backto determine if the subject's brain is in a selected state 210 beforeagain delivering TMS. For example, the method may include waiting forthe subject to experience actual rapid eye movement before deliveringanother period of TMS.

The TMS may be delivered for a fixed time period (e.g., a fraction of asecond). Alternatively, the period of time over which TMS is deliveredmay vary. For example, the period of time over which TMS is deliveredmay be based upon real time feedback from the monitoring apparatus. Themonitoring apparatus may detect the various frequencies or sleepcharacteristics that may trigger the method 200 to initiate and/ormaintain the TMS delivery step 212 or to terminate TMS delivery andreturn to the determination mode 210. The method 200 may continuouslyloop or may only loop a selected number of times. In at least oneembodiment, the number of loops the method 200 may undergo may be basedon the hours of sleep per night a subject generally sleeps, is expectedto sleep, etc.

TMS may be delivered 212 to the subject during a selected time periodwhen the subject is asleep and the electrical activity of the subject'sbrain is, for example, determined 210 to be undergoing sawtoothwaveforms before rapid eye movement. TMS may alternatively or also bedelivered during other physical and/or neurophysiological activity. Forinstance, TMS may be delivered to the subject when the subject isdetermined to be undergoing slow wave sleep (in addition to or in placeof, e.g., delivery during sawtooth wave activity).

Further, TMS may be delivered 212 to the subject during sleep when thesubject is determined 210 to be undergoing a more specific portion ofthe sleep cycle. For example, TMS may be delivered to a subject when thesubject is undergoing sleep spindles. In such a case, the TMS may bedelivered for a pre-selected fixed time period that is long enough to,e.g., deliver TMS during an entire typical sleep spindle episode.Alternatively, the period of time over which TMS is delivered may vary.For example, the period of time over which TMS is delivered may be basedon feedback, with the TMS delivery terminating when the sleep spindleepisode is over. In another example, TMS may be delivered to a subjectduring sleep spindles specifically when the subject is undergoing theshort period of stage II sleep immediately preceding rapid eye movementsleep. Again, this short section of the sleep cycle may be determined byreal time feedback from monitoring apparatus.

Further, for example, TMS may be delivered to a sleeping subject whenselected brain wave frequencies are detected. Such selected brain wavesfrequencies may correspond to various memory consolidation functions ofthe brain. For instance, TMS may be delivered to the subject based onelectrical activity of one or more selected portions of the subject'sbrain, e.g., when the selected portion(s) of the subject's brain is/areoscillating at a frequency of about 3 hertz to about 8 hertz (the thetafrequency). As described herein, the theta frequency has been seen inawake subjects while they are learning, and again, when the subjects areasleep.

In other embodiments, TMS may be delivered when selected portion(s) of asubject's brain is/are oscillating within any other selected frequencyrange. For example, TMS may be delivered when the electrical activity ofthe selected portion(s) of the subject's brain is/are oscillating atabout 26 hertz to about 70 hertz (i.e., faster frequencies observedduring REM sleep), about 0.5 hertz to about 3 hertz (i.e., frequenciesobserved during slow wave sleep), about 12 hertz to about 14 hertz(i.e., frequencies observed during sleep spindle periods), etc.

Further, the TMS may be delivered to a sleeping subject's brain duringvarious physical phenomena. For instance, TMS may be delivered to thesubject when the subject undergoes actual rapid eye movements (e.g.,monitored using EMG and/or EOG apparatus of the monitoring apparatus).In at least one embodiment, such determination is based upon on theactual eye movements, and as such, delivery of TMS may stop upontermination of the rapid eye movements. Alternatively, the TMS may bedelivered for a pre-selected fixed period of time that may, e.g., bebased on the duration of a typical period of rapid eye movement.

In at least another embodiment, the determination step 210 of method 200may include determining when the electrical activity in the subject'sbrain is indicative of an increase in slope of the 1-2 hertz slow wavewaveform of the electrical activity of slow wave sleep or when theelectrical activity in the subject's brain is indicative of an impendingincrease in slope of the waveform of the electrical activity.

The determination step 210 of method 200 may include determining theexistence of two or more conditions, which conditions may be dependentor independent from each other. For example, the method 200 may includedetermining if the subject's brain waves are undergoing sawtoothwaveforms before bursts of rapid eye movement or undergoing sleepspindles before delivering a period of TMS 212.

Determining if a subject's brain is in the proper state 210 (e.g., theoccurrence of sawtooth waves and/or phasic eye movements during REMsleep) may be accomplished utilizing monitoring apparatus positionedproximal to the subject's eye, forehead, temporalis muscle, over thefrontal lobe, over the temporal lobe, over the parietal lobe, overoccipital lobe, etc.

FIG. 3 depicts another exemplary method 300 of providing stimulationaccording to the present invention. In this method, auditory stimulusmay be delivered to the subject during an awake period and during anasleep period. The delivery of auditory stimulation when a subject isawake and then after the subject falls asleep may create an associationbetween learning tasks the subject experienced during the awake periodand the memory consolidation of such learning tasks during the asleepperiod.

In this method, auditory stimulation apparatus may be provided 302.Auditory stimulation apparatus may include, e.g., a power supply, acontrol system, a display system, headphones, speakers, tapes, compactdiscs, memory, and/or any other component as would be known by one ofordinary skill in the art. The auditory stimulation apparatus may workin conjunction with a portable audio device like, e.g., an Apple iPod, aMP3 player, a compact disc (CD) player, etc. Further, the auditorystimulation apparatus may be a non-portable audio device like, e.g., ahome stereo system, radio, etc.

A subject may configure the auditory stimulation apparatus to deliverdifferent types of auditory stimulation to, e.g., correspond todifferent types of awake learning tasks. For example, a subject mayconfigure the auditory stimulation apparatus to deliver a first type ofauditory stimulation, such as, e.g., classical music (or classical musicof a specific composer), while the subject is learning a selected typeof material (e.g., math, grammar, history, etc.). Further, for example,a subject may configure the auditory stimulation apparatus to deliver asecond type of auditory stimulation, such as, e.g., ambient “waterflowing” sounds, while the subject is learning vocabulary. Stillfurther, for example, a subject may configure the auditory stimulationapparatus to deliver a third type of auditory stimulation, such as,e.g., short auditory tones (e.g., about 1 kilohertz ore more, 2kilohertz or less, etc. for about one-half second or less, about 1second or more, about 1 second or less, etc.), that are selected tocorrespond to a selected learning activity.

More specifically, a subject may further configure the auditorystimulation apparatus to deliver different auditory stimulation for eachsub-task of the learning task. For example, a subject may configure theauditory stimulation apparatus to deliver a different short snippet(e.g., 5 seconds or less) of classical music for each math problem whilethe subject is learning math. A subject may apply these configurationsdescribed herein to the auditory stimulation apparatus, the stimulationsystem, and/or to a configuration apparatus that configures the auditorystimulation apparatus and/or stimulation system.

Further, different learning tasks or sub-tasks may be preferred to bestimulated during different periods of sleep. As such, auditorystimulations corresponding to specific learning tasks and/or sub-tasksmay only be delivered during specific periods of sleep (e.g., theauditory stimulations corresponding to motor tasks may be delivered whenthe subject is undergoing stage II sleep, or auditory stimulationscorresponding to non-motor tasks may be delivered when the subject isundergoing sleep spindles).

Still further, the stimulation system may include one or moreself-actuation inputs such that a user may self-actuate differentauditory stimulations (or visual, olfactory, somatosensory, ortranscranial magnetic stimulations) while learning. A subject utilizingthe self-actuation inputs may be able to self-actuate each of theauditory stimulations such that every learning task or sub-task may havethe same or a different auditory stimulation. The self-actuatedstimulations may be recorded by the stimulation system such that theselected stimulations may be re-delivered to the subject during, e.g.,the asleep period, specific stages of sleep, different states of thesubject, etc.

Monitoring apparatus 304 may also be provided in connection with thesystems of the present invention. The monitoring apparatus may be thesame as or similar to the monitoring apparatus as described withreference to step 104 of the method 100 depicted in FIG. 1. Further, themonitoring apparatus may be positioned proximate the subject's head 306in substantially the same way as described with reference to step 106 ofmethod 100 of FIG. 1. In at least one embodiment, the auditorystimulation apparatus and the monitoring apparatus may be integrated ina single unit. In at least another embodiment, the auditory stimulationapparatus and/or the monitoring apparatus may be an add-on, or plug-in,to an existing audio system, e.g., a portable music device. Further, inat least one embodiment, the auditory stimulation apparatus and themonitoring apparatus may be integrated into a removable adhesive patch.

The auditory stimulation apparatus may be positioned within earshot ofthe subject 308 so that the subject may hear the auditory stimulationboth during the awake period and asleep period. Although the sameauditory stimulation apparatus may be used for both the awake period andthe asleep period, different auditory stimulation apparatus may be usedduring each period. For example, a subject may use a portable audiodevice during the awake period and may use a larger or less portableaudio device, e.g., a home stereo, during the asleep period.

Although the method 300 depicted in FIG. 3 may involve positioning boththe auditory stimulation apparatus and the monitoring apparatusproximate the subject's head before delivering auditory stimulation whenthe subject is awake, other embodiments may not position the monitoringapparatus proximate the subject's head until after the auditorystimulation is delivered when the subject is awake (i.e., beforeauditory stimulation is delivered when the subject is asleep). In otherwords, the monitoring apparatus may not be positioned and/or used whilethe subject is awake.

The method may further include delivering auditory stimulation to anawake subject during a learning period. In at least one embodiment, anexample of such auditory stimulation may be short auditory snippets,e.g., various unique cell phone ring tones lasting several seconds induration, portions of songs, combinations of notes and/or frequencies,etc.

The auditory stimulation may be delivered to the subject when thesubject is awake during a selected time period, during one or moreselected time periods, or continuously. The delivery of auditorystimulation while the subject is awake may only occur while the subjectis learning a specific task. Such learning may include memorization,reading and comprehension, motor skills, verbal fluency, any otherlearning paradigm, etc.

Further, the auditory stimulation may be delivered only when the subjectis in the proper state which, e.g., may be determined by the electricalactivity in the subject's brain that indicates that the subject is in aparticular state. For example, as described herein, one such state maybe when a subject's brainwaves are operating in the theta frequency (orany other selected frequency range).

The auditory stimulation may be delivered to the subject when thesubject is asleep during a selected time period, during one or moreselected time periods, or continuously. The delivery of auditorystimulation while a subject is both awake and asleep may create anassociation between the learning task or tasks that the subjectexperienced during the awake period and the memory consolidation of suchlearning task or tasks during sleep.

For example, the method may include delivering auditory stimulation tothe subject when the subject is asleep during a memory consolidationperiod 312. In this step, the same auditory stimulation that wasdelivered to the subject while awake during the learning period may bedelivered to the subject while asleep during the memory consolidationperiod. During the asleep period, the volume of the auditory stimulationmay be adjusted as to not reach a level that may awaken the subject(which level may vary among subjects).

FIG. 4 depicts another exemplary method of providing stimulationaccording to the present invention. The steps 402, 404, 406, 408, 410and 414 are similar to the steps 302, 304, 306, 308, 310, and 312respectively, described herein with respect to FIG. 3.

The method depicted in FIG. 4, however, includes determining if thesubject is in a selected state before delivering auditory stimulation tothe subject when the subject is asleep 412. This step may allow auditorystimulation to be delivered at selected stages, or selected portions ofstages of the subject's sleep cycle as described herein. Step 412 may besubstantially the same as step 210 of method 200 of FIG. 2 except thedetermination may be made before delivering auditory stimulation insteadof TMS as described in method 200. Further, different auditorystimulation corresponding to different learning tasks may be deliveredduring while the subject is certain states, during or portions of stagesof the subject's sleep cycle. For example, the auditory stimulationcorresponding to a selected learning task or tasks (e.g., math, grammar,etc.) may be delivered while a subject's electrical activity indicatessawtooth waves of REM sleep. Further, for example, the auditorystimulation corresponding to motor skill tasks may be delivered while asubject is undergoing sleep spindles in stage II sleep.

The determination step 412 of method 400 may, for example, includedetermining if the subject is experiencing actual rapid eye movement(e.g., utilizing EMG and/or EOG apparatus of the monitoring apparatus),and if so, delivering a period of selected auditory stimulation 414.After the delivery of auditory stimulation 414, the method 400 may loopback to determine if the subject is in a selected state 412 before againdelivering auditory stimulation. For example, the method may includewaiting for the subject to experience actual rapid eye movement beforedelivering another period of auditory stimulation.

The auditory stimulation may be delivered for a fixed time period (e.g.,several seconds). Alternatively, the period of time over which auditorystimulation is delivered may vary. For example, the period of time overwhich auditory stimulation is delivered may be based upon real timefeedback from the monitoring apparatus (e.g., EEG apparatus, EMGapparatus, EOG apparatus, etc.). The monitoring apparatus may detect thevarious frequencies or sleep characteristics that may trigger the method400 to initiate and/or maintain the auditory stimulation delivery 414 orto terminate auditory stimulation delivery and return to thedetermination mode 412. The method 400 may continuously loop or may onlyloop a selected number of times. In at least one embodiment, the numberof loops the method 400 may undergo may be based on the hours of sleepper night a subject generally sleeps, is expected to sleep, etc.

For example, the monitoring apparatus may include EEG apparatus that maycontinuously sample the neural activity of the subject at any suitablefrequency, e.g., about 140 hertz or less, about 100 hertz or less, etc.to monitor the neural activity of the subject that oscillates at about0.5 hertz or more, about 2 hertz or more, about 70 hertz or less, about90 hertz or less, etc. In at least one embodiment, the EEG apparatus ofthe monitoring apparatus may monitor neural activity of the subject thatoscillates between about 0.5 hertz to about 70 hertz. Further, the rateat which the EEG apparatus of the monitoring apparatus may sample theneural activity of the subject may be selectable by, e.g., a switch oran administrator prior to attaching the stimulation patch to thesubject.

Further, EEG apparatus of the monitoring apparatus may acquire and/orstore data relating to the neural activity of the subject at selectedintervals, e.g., 1 minute of every 5 minutes, 15 seconds of every 1minute, etc. The selected interval during which data is stored may bechosen in view of the amount of data capable of being stored within thesystem.

The systems and methods described herein may monitor the neural,muscular, and/or ocular activity of the subject for a selected period oftime. As used herein, “monitor” or “monitoring” may be defined as anyactivity that includes acquiring signal activity. As such, “monitor” or“monitoring” may include recording signal activity, analyzing signalactivity, numerically transforming signal activity, providing feedbackin response to signal activity, etc.

Auditory stimulation may be delivered to the subject during a selectedtime period when the subject is asleep and the electrical activity ofthe subject's brain is, for example, determined 414 to be undergoingsawtooth waveforms before rapid eye movement. Auditory stimulation mayalternatively or also be delivered during other physical and/orneurophysiological activity. For instance, auditory stimulation may bedelivered to the subject when the subject is determined to be undergoingslow wave sleep (in addition to or in place of, e.g., delivery duringsawtooth wave activity).

Further, delivery of auditory stimulation 414 to the subject duringsleep may occur when the subject is determined 412 to be undergoing amore specific portion of the sleep cycle. For example, auditorystimulation may be delivered to a subject when the subject is undergoingsleep spindles. In such a case, the auditory stimulation may bedelivered for a pre-selected fixed time period that is long enough to,e.g., deliver auditory stimulation during an entire typical sleepspindle episode. Alternatively, the period of time over which auditorystimulation is delivered may vary. For example, the period of time overwhich auditory stimulation is delivered may be based on feedback, withthe auditory stimulation delivery terminating when the sleep spindleepisode is over. In another example, auditory stimulation may bedelivered to a subject during sleep spindles when the subject isundergoing the short period of stage II sleep immediately precedingrapid eye movement sleep. Again, this short section of the sleep cyclemay be determined by real time feedback from the monitoring apparatus.

Further, for example, auditory stimulation may be delivered to asleeping subject when selected brain wave frequencies are detected. Suchselected brain wave frequencies may correspond to various memoryconsolidation functions of the brain. For instance, auditory stimulationmay be delivered to the subject based on electrical activity of one ormore selected portions of the subject's brain, e.g., when the selectedportion(s) of the subject's brain is/are oscillating at a frequency ofabout 3 hertz to about 8 hertz (the theta frequency). As describedherein, the theta frequency has been seen in awake subjects while theyare learning and, again, when the subjects are asleep.

In other embodiments, auditory stimulation may be delivered whenselected portion(s) of a subject's brain is/are oscillating within anyother selected frequency range. For example, auditory stimulation may bedelivered when the electrical activity of the selected portion(s) of thesubject's brain is/are oscillating at about 26 hertz to about 70 hertz(i.e., the faster frequencies observed during REM sleep), about 0.5hertz to about 3 hertz (i.e., frequencies observed during slow wavesleep), about 12 hertz to about 14 hertz (i.e., frequencies observedduring sleep spindle periods), etc.

Further, the auditory stimulation may be delivered to a sleepingsubject's brain during various physical phenomena. For instance,auditory stimulation may be delivered to the subject when the subjectundergoes during actual rapid eye movements (e.g., as detected by themonitoring apparatus). In at least one embodiment, such determination isbased upon on the actual eye movements, and as such, delivery ofauditory stimulation may stop upon termination of the rapid eyemovements. Alternatively, the auditory stimulation may be delivered fora pre-selected fixed period of time that may, e.g., be based on theduration of a typical period of rapid eye movement.

In at least another embodiment, the determination step 412 of method 400may include determining when the electrical activity in the subject'sbrain is indicative of an increase in slope, is undergoing 1-2 hertzslow wave waveforms indicative of slow wave sleep, etc.

The determination step 412 of method 400 may include determining theexistence of two or more conditions. The two or more conditions may bedependent or independent from each other. Determining if a subject is ina selected state 412 (e.g., the occurrence of sawtooth waves and/orphasic eye movements during REM sleep) may be accomplished utilizingmonitoring apparatus positioned proximal to the subject's eye, forehead,temporalis muscle, over the frontal lobe, over the temporal lobe, overthe parietal lobe, over the occipital lobe, etc.

The determination step 412 of method 400 may include determining theexistence of two or more conditions, which may be dependent on eachother or independent from each other. For example, the method 400 mayinclude determining the existence of two independent conditions such assawtooth waveforms (before rapid eye movement) and sleep spindles, withthe existence of the two independent conditions triggering a period ofauditory stimulation 414. In such an embodiment, the auditorystimulation 414 could be initially triggered by either sawtoothwaveforms or undergoing sleep spindles. In another example, the method400 may include determining the existence of two independent conditionssuch as actual rapid eye movement or slow wave sleep.

In another example, the method 400 may include determining the existenceof two dependent conditions such as sawtooth waveforms and thesubsequent rapid eye movement and having the existence of the twodependent conditions triggering a period of auditory stimulation. Insuch an embodiment, the auditory stimulation 414 may be triggered bysawtooth waveforms before rapid eye movements of rapid eye movementsleep.

Such two or more condition determination steps may include any or all ofthe conditions described herein relating to neurophysiologicalinformation, physical phenomena, etc.

Although the two or more independent/dependent condition determinationsteps are discussed in reference to step 412 of method 400 depicted inFIG. 4, such two or more condition determination steps may be utilizedwith any other method described herein (e.g., the transcranial magneticstimulation method 200 depicted in FIG. 2).

FIG. 5A depicts another exemplary method of providing stimulationaccording to the present invention. The steps 502, 504, 506, and 508,are similar to the steps 302, 304, 306, and 308, respectively, describedherein with respect to FIG. 3. Step 514 is similar to step 210 describedherein with respect to FIG. 2.

The method 500 depicted in FIG. 5A, however, includes delivering a firstunique auditory stimulation to the subject when the subject is learninga first task 510 and delivering a second unique auditory stimulation tothe subject when the subject is learning a second task 512. Thedifferent auditory stimulation may be in the form of, e.g., variousunique cell phone ring tones lasting several seconds in duration,portions of songs, combinations of notes and/or frequencies, etc. Thedelivery of the first and the second unique auditory stimulation for thedifferent learning tasks during the awake period and the asleep periodmay create an association between the different learning tasks and thememory consolidation of each learning task during an asleep period.

In at least one embodiment, a specific auditory stimulation may bechosen to be played/delivered while learning a specific task, procedure,fact, relationship, etc. A different auditory stimulation may be usedfor each specific thing to be learned, but the same auditory stimulationmay be used if the same information is rehearsed more than once, so thata selected auditory stimulation may be specific to each task, procedure,fact, relationship, etc. The auditory stimulation may not only occurduring learning but should also occur during sleep, for example, duringthe sleep spindles of stage II sleep (preferably, but not necessarily,during the stage II sleep seen following slow wave sleep just prior tothe onset of REM sleep).

In at least another embodiment, a different auditory stimulation may bedelivered/played to the subject for each particular task. For example, afirst auditory stimulation may be delivered to the subject duringvocabulary memorization while a second auditory stimulation may bedelivered to the subject during fine motor tasks. Further, eachparticular task could be further defined. For example, a differentauditory stimulation may be delivered to the subject for each differentword during vocabulary memorization, or for each different type of wordduring vocabulary memorization (e.g., verbs, nouns, adjectives, etc.),or for different types of facts, e.g., dates in history withcorresponding events, or other such information that may be learned andremembered.

FIG. 5B depicts still another exemplary method of providing stimulationaccording to the present invention. The steps 552, 554, 556, 558, 560,562, and 568/568 are similar to the steps 502, 504, 506, 508, 510, 512,and 514 respectively, described herein with respect to FIG. 5.

The method 550 depicted in FIG. 5B, however, includes two determinationsteps 564, 568. The first determination step 564 may determine if thesubject's brain is in the proper state for delivering of auditorystimulation corresponding to the first learning task. For example, step564 may be monitoring the brain of the subject for sleep spindles andupon detecting sleep spindles, the step 564 may release to step 566 todeliver the one or more auditory stimulations corresponding to the firstlearning task, e.g., a motor skill task. The second determination step568 may monitor the subject for a different state corresponding to adifferent auditory stimulation for a second learning task. For example,step 568 may be monitoring the subject for rapid eye movement and upondetecting rapid eye movement, the step 568 may release to step 570 todeliver the second auditory stimulation, different from the firstauditory stimulation, that corresponds to the second learning task,e.g., visual learning task.

Although as depicted in FIG. 5B, the monitoring apparatus may only bemonitoring for the first state to trigger the delivery of the firstauditory stimulation before monitoring for the second state to triggerthe delivery of the second auditory stimulation, in other embodiments,the monitoring apparatus may monitor for all states simultaneously suchthat it can deliver the corresponding auditory stimulation for eachstate when the subject undergoes such state. For example, a singledetermination step may exist for detecting a first state and a secondstate. Regardless of the detection of the first state, if the secondstate is detected, the second stimulation may be delivered.

Although the steps in the methods depicted in FIGS. 1-5 are listedand/or described in a specific order, the sequences of steps maydifferent than described herein as would be known by one of ordinaryskill in the art. For example, providing monitoring apparatus 304 andpositioning the monitoring apparatus 306 as depicted in FIG. 3 may occurafter delivering auditory stimulation to the subject when the subject isawake 310.

In at least another embodiment according to the present invention, thesubject may self-actuate the auditory stimulations during the learningperiod. For example, the stimulation system may have one or moreself-actuation inputs such that while a subject is learning one or morelearning tasks, the subject may actuate the stimulation system todeliver one or more stimulations (e.g., auditory stimulations orolfactory stimulations). The subject may choose to deliver the same ordifferent stimulation for each subject, fact, and/or task. For example,a subject may press a self-actuation button (or use some other actuationinput such as, e.g., a touch screen, microphone, foot switch, keyboard,etc.) to deliver 10 second (same or different) auditory stimulation foreach math problem that the subjects learns and may press a differentself-actuation button to deliver 5 second (same or different) visual andauditory stimulation for each history fact that the subject is learning.Each stimulation that was delivered to the subject during the learningperiod may be stored on the stimulation system such that the stimulationsystem may deliver all of the stimulations that were delivered duringthe learning period to the subject during the sleep period. In one ormore embodiments, each stimulation may be delivered during a selectedstage of sleep, state of the subject, etc. as described herein

FIG. 6 is a diagrammatic representation of one exemplary transcranialstimulation system 600 according to the present invention. The system600 includes monitoring apparatus 602 and TMS apparatus 604. Themonitoring apparatus 602 may be the same as or similar to the monitoringapparatus as described with reference to step 104 of the method 100depicted in FIG. 1. The TMS apparatus may be the same as or similar tothe TMS apparatus as described with reference to step 102 of the method100 depicted in FIG. 1.

The transcranial stimulation system 600 may further include a controller606. The controller 606 may interface with the monitoring apparatus 602and the TMS apparatus 604. The controller 606 may be a microcontroller(e.g., PIC microcontroller), or any other electrical controller, thatmay include one or more central processing units, I/O ports (e.g.,serial ports, USB ports), volatile memory, nonvolatile memory, clockgenerators, analog-to-digital converters, etc. At least one input of thecontroller 606 may receive data, e.g., one or more signals, from themonitoring apparatus 602. Such data may be indicative of the specificsleep stage or sleep phenomena the subject is currently undergoing, ormay be simply raw data from the electrodes of the monitoring apparatus602. The controller 606 may further include one or more self-actuationinputs for self-actuating TMS to be delivered to the subject during thelearning period.

At least one output of the controller 606 may be coupled to the TMSapparatus 604 so that the controller may initiate and terminate thedelivery of TMS to the subject. The controller 606 may deliver TMS tothe subject based on the data it receives from the monitoring apparatus602 as described herein with respect to the methods depicted in FIGS.1-2.

Although not shown, the transcranial stimulation system 600 may includea power source, e.g., a battery, line source (e.g., power cord), fuelcell, etc.

FIG. 7 is a diagrammatic representation of one exemplary auditory/visualstimulation system 700 according to the present invention. The auditorystimulation system 700 may include monitoring apparatus 702, auditorystimulation apparatus 704, visual stimulation apparatus 706, and acontroller 708. The monitoring apparatus 702 may be the same as orsimilar to the monitoring apparatus as described with reference to step104 of the method 100 depicted in FIG. 1. The auditory stimulationapparatus may be the same as or similar to the auditory stimulationapparatus as described with reference to step 302 of the method 300depicted in FIG. 3. The controller 708 may be the same as or similar tothe controller as described with reference to the controller 606 ofsystem 700 depicted in FIG. 7.

The controller 708 may further include one or more self-actuation inputssuch that a subject may self-actuate the auditory stimulation apparatus704 and/or visual stimulation apparatus 706. For example, a subject mayself-actuate one or more visual stimulations during each learning taskthe subject is learning that is associated with memory tasks. Thecontroller 708 may record or track the visual and/or auditorystimulations delivered to the subject during the learning period suchthat the visual and/or auditory stimulations may be again delivered tothe subject when the subject is sleep, e.g., during the appropriatestages of sleep corresponding memory consolidation.

The visual stimulation apparatus 706 may provide visual stimulation tothe subject (e.g., stimulate the subject's eyes through closed eyelids).The visual stimulation apparatus 706 may be any apparatus capable ofdelivering visual stimulation. For example, the visual stimulationapparatus 706 may include light emitting diodes (LED), liquid crystaldisplays (LCD), organic light emitting diodes (OLED), incandescent lightsources, electroluminescent light sources, etc. The visual stimulationapparatus 706 may include apparatus for holding the visual stimulationapparatus 706 proximate the subject's eyes (e.g., goggles, glasses,headbands, hats, etc.). Further, the visual stimulation apparatus 706may be spaced from the subject's eyes and positioned such that itdirects the visual stimulation towards the subject's eyes. The visualstimulation may be delivered such that the stimulation is receivablethrough the subject's eyelids for, e.g., an asleep period, or an awakeperiod where the subject closes their eyes. The visual stimulation mayinclude flashing lights, still images, movie clips, animations, etc.Visual stimulation may include any visible activity (typically, lighthaving a wavelength of about 400-700 nanometers). Further, the visualstimulation, e.g., flashing lights, may vary in frequency, duration,pattern, and/or intensity.

Although not depicted, the auditory/visual stimulation system 700 mayinclude a storage medium, e.g., flash memory, a hard drive, a CD-ROM,etc., for storing various unique auditory stimulation. Such storagememory may be removable and interchangeable as to, e.g., be programmedand/or loaded by a personal computer. Further, the auditory/visualstimulation system 700 may include an auditory output device such as,e.g., headphones, speakers, etc.

In at least one embodiment, the TMS system 600 and the auditory/visualstimulation system 700 may be combined and used in conjunction with eachother utilizing, e.g., the methods described herein and depicted inFIGS. 1-5, etc. In other words, the stimulation delivered may includeone or more of TMS, auditory stimulation, and/or visual stimulation. Thecombination of one or more of TMS, auditory stimulation, and visualstimulation may always be delivered together or they may be selectivelycombined. Further, the one or more of TMS, auditory stimulation, and/orvisual stimulation may be delivered simultaneously and/or sequentially.

FIG. 8 is an illustrative view of one exemplary embodiment of astimulation system 800 being used with subject 801. Stimulation system800 includes apparatus 802 that includes monitoring apparatus (e.g., EEGapparatus) and TMS apparatus. An electrode 804 is attached to theforehead of the subject 801 and is electrically coupled to the apparatus802. The electrode 804 may transmit a signal to the apparatus 802 to,e.g., measure the electrical activity of the subject's brain.Illustrative waves 806 are shown to represent TMS that may be deliveredfrom the apparatus 802 to the subject 801 as described herein. Further,some components that may be included in TMS systems according to thepresent invention may be described in U.S. Patent Application Pub. No.2008/0081941 A1, published on Apr. 3, 2008, and entitled “Method andApparatus for Promoting Restorative Sleep.”

FIG. 9A is an illustrative view of another exemplary embodiment of astimulation system 900 being used with subject 901. Stimulation system900 includes apparatus 902 that includes monitoring apparatus andauditory stimulation apparatus. An electrode 904 is attached to theforehead of the subject 901 and is electrically coupled to the apparatus902. The electrode 904 may transmit a signal to the apparatus 902 tomeasure, e.g., the electrical activity of the subject's brain, themuscular activity of the subject's temporalis muscle, etc. Headphones906 are connected to the apparatus 902 and located proximate thesubject's ears for delivering auditory stimulation from the apparatus902 to the subject 901 as described herein.

FIG. 9B is an illustrative view of another exemplary embodiment of astimulation system 920 being used with subject 921. Stimulation system920 includes a stimulation patch 922 that includes monitoring apparatus,auditory stimulation apparatus, and visual stimulation apparatus. One ormore electrodes may be located on the rear side (not shown—see FIG. 11for a rear view of an exemplary stimulation patch) of the patch 922. Asshown, the patch 922 is attached to the forehead of the subject 921,although other placement locations may be envisioned.

The patch 922 may be attached to the forehead of the subject 921 usingadhesive on the interior surface of the patch, i.e., the surface facingthe subject's forehead. The adhesive may preferably be anyskin-compatible, pressure-sensitive adhesive that may adhere to asubject and that may be removed without significantly damaging thesubject's skin. Further, the adhesive and/or the patch 922 may includeapertures such that the patch 922 is “breathable.” Also, the adhesiveand/or patch 922 may be flexible so that it may conform to unevensurfaces, such as a subject's forehead. The adhesive may cover,partially cover, or not cover the electrodes. In at least oneembodiment, the adhesive may be thinner over the electrodes than theremainder of the patch 922 such that sufficient conductivity can beobtained between the electrodes and the subject's skin. In at least oneembodiment, the adhesive may be in the form of an adhesive pad orcushion. A non-stick, protective backing material may be located overthe adhesive of the patch that may be peeled-off before attaching thepatch to a subject. The patch may be able to sense when the backingmaterial is removed from patch and thereby turn “on” the patch.Attaching the patch to a subject may include peeling a protective layerfrom the adhesive surface of the patch, locating the patch proximate tothe portion of the subject to be monitored, and applying the patch tothe portion of the subject (e.g., forehead, temple, etc.). In otherembodiments, a user may apply an adhesive substance to the rear side ofthe patch before applying the patch to the subject.

Speaker 926 may be connected to the stimulation system 900 and locatedproximate the subject's ear for delivering auditory stimulation from thepatch 922 to the subject 921 as described herein.

The patch of FIG. 9B also includes visual stimulation devices 924. Asdepicted, the visual stimulation devices 924 may be one or morelight-emitting devices (such as, e.g., a pair of light-emitting diodes).The visual stimulation devices 924 may emit one or more colors of lightof varying brightness, frequency, intensity, etc.

The patch 922 may further include a memory device slot 928 and a memorydevice 930. The memory device 930 may be any non-volatile storagedevice. It may be preferred that the memory device 104 be in the form ofa flash memory device, such as, e.g., Compact Flash (CF), MultiMediaCard (MMC), Secure Digital (SD), Memory Stick, xD, RS-MMC, miniSD,microSD, Intelligent Stick, etc. In other embodiments, the system mayinclude a non-removable storage device. Further, in at least anotherembodiment, the system may include a volatile storage device.

The memory device slot 928 may be a slot designed to receive the memorydevice 930. When the memory device 930 is inserted into the memorydevice slot 928 (as shown), the electrical contacts of the memory device930 may contact the electrical contacts of the memory device slot 928 toallow communication between the memory device and other componentry ofthe system 920. In at least one embodiment, the memory device 930 mayfit within the memory device slot 928 with an interference fit. Further,in at least another embodiment, the slot 928 may include a latch oranother retention device for securing the memory device 930 within theslot 928.

The memory device slot 928 may be electrically coupled to the electroniccomponentry of the system 920 such that data may be stored on the memorydevice 930. As described herein, “electrically coupled” may be anyelectrical connection, e.g., using a conductive material such as wireconnection, flexible circuit board, printed circuit board, etc.

The stimulation patch 920 may further include one or more input buttons932. A user may depress the input buttons 932 to perform a variety offeatures with the stimulation system 920. For example, a user may userthe input buttons 932 to enable or disable various components of thestimulation system (e.g., auditory stimulation apparatus, visualstimulation apparatus, monitoring apparatus, etc.), alter variousparameters of the monitoring apparatus (e.g., sensitivity, samplingrate, filters, etc.), change the auditory stimulation being delivered,electronically mount or un-mount the memory device, alter variousparameters of the auditory stimulation (e.g., volume, frequency, bass,treble, etc.), alter various parameters of the visual stimulation (e.g.,pattern, intensity, color, duration, brightness, frequency, etc.), etc.In the embodiment depicted in FIG. 9B, the buttons are triangular shapedto, e.g., indicate up and down arrows. In other embodiments, however,the buttons may be multiple shapes and sizes. Further, in otherembodiments, the system 920 and/or patch 922 may include multiplebuttons (e.g., three or more buttons). Further, although this embodimentdepicts depressible buttons, input buttons according to the presentinvention may be any input device, e.g., switches, toggles, touchscreens, etc.

Although not depicted, the stimulation system 920 may further includeother componentry that may be required to monitor the state of thesubject and deliver auditory and/or visual stimulation to the subjectincluding, e.g., electronic apparatus, power switches, power sources,indicator lights, etc.

The one or more input buttons 932 may be self-actuation inputs.Self-actuation inputs may be used to deliver one or more stimulations tothe subject at the subject's control. For example, the subject maydepress one of the input buttons 932 to deliver a unique auditorystimulation (e.g., a 5 second tone). The stimulation system 920 may thenrecord what auditory stimulations were delivered during the learningperiod such that they may be delivered to the subject while the subjectis sleeping, e.g., during a specific sleep stage. The self-actuationinputs may further be utilized to change the type of auditorystimulation or type of stimulation (auditory, visual, etc.) to bedelivered. For example, a subject may be utilizing auditory stimulationsconsisting of classical music for history memorization problems and uponswitching to learning Spanish language study may want to change theauditory stimulations to ambient noise (e.g., water gurgling) or maywant to change to visual stimulations (e.g., faint blue light).

For example, stimulation system may be turned “on” using a power switchthat may be any kind of two or more position switch. The power switchmay be electrically coupled to electronic apparatus, a power supply,etc. The power switch may have more than two positions for differentmodes of operation of the stimulation system. For example, the powerswitch may have three positions: “awake,” “asleep,” and “off.” When thepower switch is in the “awake” position, the stimulation system may becapable of delivering auditory stimulation the subject eitherautomatically (e.g., the system may automatically deliver auditorystimulation), semi-automatically (e.g., the system may automaticallydeliver auditory stimulation and the user may manually change the typeof auditory stimulation), and/or manually (e.g., the user may start andstop the auditory stimulation and may change type of auditorystimulation). When the power switch is in the “asleep” position, thestimulation system may monitor the state of the subject and deliverauditory stimulation when the subject is in the proper state. When thepower switch is in the “off” position, the stimulation patch may bedormant.

Further, for example, the power switch may have a position for a“download” mode in which data may be transferred to and from thestimulation system. Also, in other embodiments, the stimulation patchmay be turned “on” by attaching the patch to a subject's forehead (e.g.,the patch may include electrodes capable of sensing when the patch iscontacting skin—at which time, apparatus on the patch may be turned“on”).

Also, the stimulation patch may further include an indicator light. Theindicator light may be a single LED. In at least one embodiment,however, the indicator light may consist of one or more LEDs, OLEDs,and/or LCDs. The indicator light may indicate to the user the mode orstate of the stimulation patch. For example, if the indicator light is“on,” then the indicator light may be indicating that the stimulationpatch is monitoring, e.g., EEG signals from the electrodes and storingsuch signals on the memory device. Also, for example, the indicatorlight may “blink” to indicate the power source is running low on power.

FIG. 9C is an illustrative of view of another exemplary embodiment of astimulation system 940 being used with subject 941. Stimulation system940 includes a stimulation patch 942 that includes monitoring apparatus,auditory stimulation apparatus, and visual stimulation apparatus. One ormore electrodes may be located on the rear side (not shown) of the patch942. As shown, the patch 942 is attached to the forehead of the subject941 using, e.g., adhesive.

The patch further includes one or more visual stimulation devices 944similar to those described with respect to the embodiment depicted inFIG. 9B.

The stimulation patch 942 further includes power source 948 andelectronic apparatus 950. The power source 948 may be a watch battery,fuel cell, etc. The electronic apparatus 950 may include amicrocontroller, microprocessors, EEG apparatus, EMG apparatus, EOGapparatus, power management units, analog-to-digital converters, digitalsignal processors, input/output (I/O) ports, etc. The electronicapparatus 950 may include an I/O port that is electrically coupled to,e.g., a memory device slot. Such electrical coupling may be in the formof any suitable interface, e.g., serial data connection, parallel dataconnection, Advanced Technology Attachment (ATA), Small Computer SystemInterface (SCSI), Serial Advanced Technology Attachment (SATA),Universal Serial Bus, IEEE 1394, etc. Further, such electrical couplingmay be utilized to couple the stimulation patch 942 to a configurationapparatus, e.g., a personal computer.

The monitoring apparatus may be integrated with the electronic apparatus950 on a single microchip. In other embodiments, the electronic and/ormonitoring apparatus may include multiple electronic componentselectrically coupled to each other on, e.g., a printed circuit board. Inat least one embodiment, the electronic apparatus including monitoringapparatus may be attached to a flexible circuit board. The I/O ports ofthe monitoring apparatus may be electrically coupled to the one or moreelectrodes. The one or more electrodes may transmit an electricalsignal. The electrical signal may be an analog signal which may beconverted to digital data with an analog-to-digital converter. Digitaldata representative of the analog signal may be stored on, e.g., amemory device. In other embodiments, an analog signal from the one ormore electrodes may be stored on a storage apparatus, e.g., magnetictape, etc.

The stimulation patches according to the present invention may bedescribed as being “self-contained.” As used herein, a self-containedstimulation patch may be defined as having all parts necessary for itsoperation (e.g., monitoring apparatus, apparatus, electronic apparatus,etc.) located within or on the patch itself (e.g., the substrate of thepatch).

The auditory stimulation apparatus of the stimulation system 940 mayinclude a speaker 946 as shown emitting “sound waves” in FIG. 9C.Although this embodiment only includes a single speaker, the stimulationsystems according to the present invention may include two or morespeakers. In at least one embodiment, the stimulation system includes apatch that when attached a subject extends across the subject's foreheadfrom the left temporalis muscle to the right temporalis muscle andincludes a speaker at either end of the patch for emitting auditorystimulation to each ear (e.g., patch 1150 depicted in FIG. 12).

Although the embodiments described above utilize either TMS apparatus,visual stimulation apparatus, and/or auditory stimulation apparatus, themethods and/or systems according to the present invention may utilizeany other type of stimulation apparatus in place of or in addition toTMS apparatus, visual stimulation apparatus, and/or auditory stimulationapparatus. Further, each component of the systems depicted in FIGS.9A-9C may be utilized on any of the systems depicted in FIGS. 9A-9C(although not necessarily shown or described with reference to thatparticular system).

FIG. 10 is a diagrammatic representation of one exemplary stimulationsystem 1000 that includes a controller 1002, adhesive 1003 (e.g., toattach a stimulation patch to a subject), a power supply 1004, storageapparatus 1005, monitoring apparatus 1006, and stimulation apparatus1008.

The monitoring apparatus 1006 includes EEG apparatus 1010, EMG apparatus1012, and/or EOG apparatus 1014. Each of the monitoring apparatus mayinclude one or more electrodes to be locate adjacent the subject tomonitor various parameters that may indicate when the subject is in theproper state for stimulation to be delivered to the subject.

The EEG apparatus 1010 may include microcontrollers, microprocessors,analog-to-digital converters, digital signal processors, I/O ports, etc.The EEG apparatus 1010 may be capable of recording the neural activityof electrical potential across cell membranes. The changes in electricalpotential in the cortex contain rhythmical activity, which typicallyoccur at frequencies of about 0.5 hertz to about 70 hertz. The EEGapparatus 1010 may continuously sample the neural activity of thesubject at about 100 hertz or less, 60 hertz or less, etc. and maymonitor the neural activity of the subject that oscillates between about0.5 hertz or more, about 70 hertz or less, etc. In at least oneembodiment, the EEG apparatus 1010 may monitor the neural activity ofthe subject that oscillates between about 0.5 hertz to about 70 hertz.Also, the EEG apparatus 1010 may monitor the neural activity of thesubject at selected intervals, e.g., 1 minute for every 5 minutes or 15seconds for every 1 minute.

The EMG apparatus 1012 may include microcontrollers, microprocessors,analog-to-digital converters, digital signal processors, I/O ports, etc.The EMG apparatus 1012 may be capable of recording the muscular activityof electrical potential across muscular membranes. Changes in electricalpotential in muscular membranes may oscillate between about 10 hertz ormore, about 90 hertz or less, etc. depending on the size of the muscle,the type of muscle, etc. The EMG apparatus 1012 may sample the muscularactivity of the subject at about 180 hertz or less, about 100 hertz orless, etc., and may monitor the muscular activity of the subject thatoscillates at about 0.5 hertz or more, about 10 hertz or more, about 90hertz or less, about 180 hertz or less, etc. Further, the rate at whichthe EMG apparatus 1012 may sample the muscular activity of the subjectmay be selectable by, e.g., a switch or an administrator prior toattaching the stimulation patch. In at least one embodiment, the EMGapparatus 1012 may monitor the muscular activity of the temporalismuscle and/or frontalis muscle of a subject that corresponds to REMsleep, e.g., the muscular activity of the temporalis muscle and/orfrontalis muscle that oscillates at about 10 hertz or more, about 90hertz or less, etc. Further, the EMG apparatus 1012 may measureelectrical potential at about 25 microvolts or more, about 50 millivoltsor less, etc.

The EOG apparatus 1014 may include microcontrollers, microprocessors,analog-to-digital converters, digital signal processors, I/O ports, etc.The EOG apparatus 1014 may be capable of recording the ocular activityof a subject. Changes in electrical potential near the subject's eye asa result of ocular activity may oscillate between about 0.5 hertz andabout 200 hertz. The EOG apparatus 1014 may sample the ocular activityof the subject at about 180 hertz or less, about 100 hertz or less,etc., and may monitor the ocular activity of the subject that oscillatesat about 0.5 hertz or more, about 2 hertz or more, about 100 hertz orless, about 200 hertz or less, etc. Further, the rate at which the EOGapparatus 1014 may sample the ocular activity of the subject may beselectable by, e.g., a switch or an administrator prior to attaching thestimulation system. EOG monitoring may be limited to periods when theEEG apparatus and/or EMG apparatus indicate that a subject is sleeping.

The stimulation apparatus 1008 may include auditory stimulationapparatus 1016, TMS apparatus 1018, visual stimulation apparatus 1020,somatosensory stimulation apparatus 1022, and/or olfactory stimulationapparatus 1024. The auditory stimulation apparatus 1016, the TMSapparatus 1018, and the visual stimulation apparatus 1020 may besubstantially similar to the auditory stimulation apparatus, TMSapparatus, and visual stimulation apparatus as previously describedherein.

The somatosensory stimulation apparatus 1022 may physically stimulate asubject (e.g., stimulate a subject's arm). The somatosensory stimulationapparatus 1022 may include vibratory apparatus, compression apparatus,acupuncture apparatus, thermal apparatus (heating and/or cooling), etc.The somatosensory stimulation apparatus 1022, however, may be anyapparatus capable of delivering any type of somatosensory stimulation.The somatosensory stimulation apparatus 1022 may be located anywhereproximate the subject's body such that it may deliver somatosensorystimulation to the subject. In at least one embodiment, thesomatosensory apparatus 1022 may be a sleeve that may be positionedaround an appendage (e.g., arm, leg, finger, etc.) of the subject.Further, the somatosensory apparatus 1022 may be spaced away fromsubject such that only the actual somatosensory stimulation contacts thesubject (e.g., warm air). The somatosensory stimulation may includevibrations, compressions, warm air, cool air, humid air, electricalcurrent, pinching, rubbing, etc. In at least one embodiment, thesomatosensory stimulation, e.g., compressions and/or vibrations, mayvary in frequency, duration, pattern, and/or intensity.

The olfactory stimulation apparatus 1024 may provide aromaticstimulation a subject by, e.g., delivering one or more scents to thesubject. The olfactory stimulation apparatus 1024 may be locatedanywhere proximate the subject's body such that it may effectivelydeliver the olfactory stimulation to the subject. In at least oneembodiment, the olfactory apparatus 1024 may be worn around thesubject's neck. Further, the olfactory apparatus 1024 may be spaced awayfrom subject (i.e., the olfactory apparatus 1024 does not contact thesubject) such that only the actual olfactory stimulation contacts thesubject (e.g., the olfactory apparatus may be similar to an airfreshener plugged into an outlet of a wall). Also, one or more distinctscents may be provided by the olfactory stimulation apparatus 1024.

The stimulation delivered from the stimulation apparatus 1008 may bedelivered during a selected time period, during one or more selectedtime periods, or continuously. Further, the stimulation apparatus 1008may deliver stimulation at different time periods from one another. Inat least one embodiment, the delivery of stimulation while the subjectis awake may only occur while the subject is learning a specific task.Such learning may include memorization, reading and comprehension, motorskills, verbal fluency, any other learning paradigm, etc. Further, thedelivery of stimulation while the subject is awake may only occur whenthe electrical activity in the subject's brain indicates that thesubject is in a particular state. For example, as described herein, onesuch state may be when a subject's hippocampal brainwaves are operatingin the theta frequency (or any other selected frequency range).

Also, the stimulation may be delivered to the subject when the subjectis asleep during a selected time period, during one or more selectedtime periods, or continuously. The delivery of the stimulation while asubject is both awake and asleep may create an association between thelearning task and/or tasks that the subject experienced during the awakeperiod and the memory consolidation of such learning task or tasksduring sleep.

The controller 1002 may include multiple inputs, e.g., self-actuationinputs. The self-actuation inputs may allow a subject to self-actuatethe delivery of unique stimulation (e.g., auditory, visual, olfactory,somatosensory, or transcranial magnetic stimulation) to the subject asdescribed herein.

The controller 1002, adhesive 1003 (e.g., to attach a stimulation patchto a subject), a power supply 1004, storage apparatus 1005, monitoringapparatus 1006, and stimulation apparatus 1008 may be a single, integralunit, or may be multiple interconnected units. Further, the stimulationapparatus 1008 and/or monitoring apparatus 1006 may be used inaccordance with any method described herein including the methodsdepicted in FIGS. 1-5. Such methods include delivering stimulation to asubject when the subject is determined to be undergoing a specificportion of the sleep cycle, delivering stimulation to a subject for aselected time period, delivering stimulation to subject when theelectrical activity of the subject's brain is undergoing a specificfrequency, etc.

Furthermore, each of the stimulation apparatus 1008 and other apparatus,systems, and methods described herein may be used any combinationwhatsoever. For example, a stimulation system according the presentinvention may include a controller, a power system,electroencephalography apparatus, TMS apparatus, and olfactoryapparatus.

A rear view of a stimulation patch 1100 is depicted in FIG. 11. Thestimulation patch 1100 may be similar to the stimulation patch 922depicted in FIG. 9B. This view shows the electrodes of the stimulationpatch 1100. For example, stimulation patch 1100 includes monitoringapparatus having EEG electrodes 1102 located to correspond to asubject's temporal lobes, EEG electrodes 1104 located to correspond to asubject's frontal lobes, EMG electrodes 1106 located to correspond to asubject's temporalis muscle, EOG electrodes 1108 located to correspondto a subject's ocular cavity, and reference electrodes 1110. Further,the stimulation patch 1100 may include EEG, EMG, and EOG apparatus(although not depicted) to monitor and collect data from the electrodes.Since FIG. 11 depicts the rear view of a stimulation patch, i.e., thesurface that will be adhered to the subject, the surface may includeadhesive.

Although multiple electrodes are depicted for each type or class, onlyone electrode may be required at each location. The use of multipleelectrodes provides redundancy (if, e.g., an electrode loses contact, anelectrode malfunctions, etc.). Also, any of the electrodes on the patchmay be used as a reference electrode (if, e.g., the use of a differentelectrode provides a better reference signal, a reference electrodemalfunctions, etc.).

A front view of a stimulation patch 1150 is depicted in FIG. 12.Stimulation patch 1150 may be similar to the stimulation patchesdescribed herein except that the stimulation patch 1150 may sized andshaped to extend across the forehead of a subject from a first end 1154to a second end 1156. Each end 1154, 1156 may correspond to a subject'stemporalis muscle (e.g., to be monitored by monitoring apparatus havingelectrodes located at either end 1154, 1156) and may include an auditorystimulation output device, e.g., a speaker 1152. In at least oneembodiment, the patch 1150 may include multiple electrodes locatedthroughout the patch 1150 to monitor any portion of the subject's head.

FIG. 13 is a diagrammatic representation of one exemplary embodiment ofa configuration system 1300 according to the present invention. Theconfiguration system 1300 may be utilized by a user to analyze toprogram and/or configure the stimulation systems described herein. Auser may utilize the configuration system 1300 to configure thestimulation system with specific “play” lists, genres (e.g., jazz,hip-hop, classical, etc.), auditory types (e.g., ambient noise, whitenoise, etc.), visual stimulation parameters, olfactory stimulationparameters, somatosensory stimulation parameters, etc. Suchconfiguration may further include uploading auditory stimulation, e.g.,digital music files, to the stimulation system.

In at least one embodiment, the user may select the type of stimulation(e.g., auditory, transcranial magnetic, visual, olfactory, orsomatosensory stimulation) to correspond to each different type oflearning task using the configuration apparatus. As such, the user maymerely select a learning task on the stimulation system (e.g., patch)and the system may automatically deliver the stimulation the useralready selected to correspond to the learning task. Further, a set ofstimulations may be selected to correspond to each learning task suchthat each sub-task (e.g., each problem of a set of math problems) mayhave a unique stimulation. After a set of stimulations is selected toeach learning task, a user may select the learning task and uponbeginning each sub-task, the user may self-actuate to deliver one of theset of stimulations corresponding to the learning task. Furthermore, auser may be able change learning tasks during the learning period suchthat a different stimulation or set of stimulations corresponding to thenew learning task may be delivered through, e.g., self-actuation.

The configuration system 1300 may include a processing apparatus 1302,an input interface 1304, an output interface 1306, and a power supply(not depicted). The configuration system 1300 may be a personal computerrunning an operating system such as Microsoft Windows, GNU/Linux, AppleOS X, etc. In other embodiments, the configuration system 1300 may be apersonal data assistant (PDA), a laptop computer, a cellular telephone,an ultra-mobile personal computer (UMPC), etc.

The input interface 1304 may be an interface designed to receive thedata recorded the monitoring apparatus of the stimulation systemsdescribed herein. Further, the input interface 1304 may include a slotfor receiving a removable memory device such as the memory device 930 ofFIG. 9B. In other embodiments, the input interface 1304 may be an I/Oport such as a serial data port, a parallel, data port, a USB data port,etc. that may be connectable to the storage device of the stimulationpatch and/or any input peripheral (e.g., mouse, keyboard, touch screen,etc.) for use a by a user. In these embodiments, a data transmissioncable (e.g., a USB cable) may be connected to the input interface 1304of the configuration system 1300 and to the stimulation system toconfigure the stimulation system.

The output interface 1306 may be any display, e.g., a liquid crystaldisplay, cathode ray tube display, etc., that may be capable ofdisplaying a configuration menu to a user to configure the stimulationsystem using the configuration apparatus 1304.

FIG. 14 is a diagrammatic representation of a configuration of astimulation system. The representation shows sets of stimulation 1400,learning tasks 1410, and sleep states/stages 1420. Each set of the setsof stimulation 1400 may be associated with one or more of the learningtasks 1410. Each learning task of the learning tasks 1410 may beassociated with one or more sleep states/stages 1420.

For example, the first set of auditory stimulations 1401 may beassociated with math problems 1411. The first set of auditorystimulations 1401 may include one or more auditory stimulations (e.g.,that a user may self-actuate to deliver an auditory stimulation from thefirst set of auditory stimulations for each math problem during theawake period). Every auditory stimulation delivered to the subjectduring the awake, learning period may then be associated with slow wavesleep 1424 such that when a subject undergoes slow wave sleep, one ormore of the auditory stimulations (from the auditory stimulationsdelivered during the awake period) may be delivered to the subject,e.g., consecutively, etc.

Further, for example, the second set of visual stimulations 1404 isassociated with vocabulary memorization 1414. The second set of visualstimulations 1404 may include one or more visual stimulations (e.g.,that a user may self-actuate to deliver a visual stimulation from thesecond set of visual stimulations for each word studied during the awakeperiod). Every visual stimulation delivered to the subject during theawake, learning period may then be associated with sleep spindle 1422and the period immediately preceding slow wave sleep 1425 such that whena subject undergoes sleep spindles or the period immediately precedingslow wave sleep, one or more of the visual stimulations (from the visualstimulations delivered during the awake period) may be delivered to thesubject, e.g., consecutively.

Although FIG. 14 is merely a diagrammatic representation of oneexemplary configuration of the stimulation systems as described herein,a user interface (e.g., run by a computer program) on configurationsystem 1300 as described herein reference to FIG. 13 may look similar tothe diagrammatic representation in FIG. 14. A subject may use such userinterface (e.g., using any input device such as a touch screen, mouse,keyboard, etc.) to select the set of stimulations to correspond to eachlearning task, and the learning tasks to correspond to each sleepstate/stage. Further, such user interface may include the individualstimulations of the set of stimulations so that a subject may evenfurther specifically tailor the stimulation system.

For example, a subject may have noticed while learning history that thesubject has a difficult time remembering the date of the forming of theUnited Nations. As such, the subject may use the configuration systemand user interface to deliver the stimulation that was delivered whilethe subject was learning the date of the forming of the United Nationsduring two or more sleep states/stages (while leaving rest of thestimulations corresponding to each history fact to be delivered duringonly one sleep state/stage).

FIG. 15 is a diagrammatic representation of one exemplary embodiment ofa stimulation system 1500 according to the present invention. Thestimulation system 1500 may include a learning component 1510 and aconsolidation component 1520. The learning component 1510 may includeTMS apparatus 1511, auditory stimulation apparatus 1512, visualstimulation apparatus 1513, olfactory stimulation apparatus 1514,somatosensory stimulation apparatus 1515, and one or more self-actuationbuttons 1516. The consolidation component 1520 may include TMS apparatus1521, auditory stimulation apparatus 1522, visual stimulation apparatus1523, olfactory stimulation apparatus 1524, somatosensory stimulationapparatus 1525, a controller 1526, and monitoring apparatus 1527.

The learning component 1510 may be utilized by a subject during alearning period while the consolidation component 1520 may be utilizedby a subject during a sleeping period. Both the learning component 1510and consolidation component 1520 may be similar to any apparatus and/orsystem described herein and further may utilize any method describedherein.

Although the learning component 1510 and the consolidation component1520 are part of the stimulation system 1500, the learning component1510 may be a component of a first unit and consolidation component 1520may be a component of a second unit different and separate from thefirst unit. In this embodiment, a subject can utilize the learningcomponent 1510 without the consolidation component 1520 during thelearning period. Likewise, the subject can utilize the consolidationcomponent without the learning component 1520 during the sleepingperiod. Further, in other embodiments, the learning component 1510 andthe consolidation component 1520 may be components of a single integralunit.

The complete disclosure of the patents, patent documents, andpublications cited in the Description of Exemplary Embodiments, andelsewhere herein are incorporated by reference in their entirety as ifeach were individually incorporated.

Illustrative embodiments of this invention are discussed and referencehas been made to possible variations within the scope of this invention.These and other variations and modifications in the invention will beapparent to those skilled in the art without departing from the scope ofthe invention, and it should be understood that this invention is notlimited to the illustrative embodiments set forth herein. Accordingly,the invention is to be limited only by the claims provided below andequivalents thereof.

1. A stimulation system for stimulating a subject, the systemcomprising: a learning component and a consolidation component, whereinthe learning component comprises: auditory stimulation apparatus fordelivering one or more selected auditory stimulations to the subject;and one or more self-actuation inputs operably coupled to the auditorystimulation apparatus for self-actuation by the subject to deliver atleast one selected auditory stimulation of the one or more selectedauditory stimulations to the subject; and wherein the consolidationcomponent comprises: monitoring apparatus for monitoring the sleep stateof a subject, wherein the monitoring apparatus optionally comprises oneor more electrodes; auditory stimulation apparatus for delivering one ormore selected auditory stimulations to the subject; and a controlleroperably coupled to the monitoring apparatus to receive input regardingthe sleep state of the subject from the monitoring apparatus andoperably coupled to the auditory stimulation apparatus to operate theauditory stimulation apparatus, wherein the controller utilizes theinput from the monitoring apparatus to determine when the subject is inone or more selected sleep states, and further wherein the controlleroperates the auditory stimulation apparatus to deliver at least oneselected auditory stimulation of the one or more selected auditorystimulations previously delivered by the learning component to thesubject during at least one selected sleep state of the one or moreselected sleep states.
 2. The stimulation system of claim 1, wherein thelearning component and the consolidation component are components of asingle integral unit.
 3. The stimulation system of claim 1, wherein thelearning component is a component of a first unit, wherein theconsolidation component is a component of a second unit, and wherein thesecond unit is separate from the first unit.
 4. The system of claim 1,wherein the monitoring apparatus comprises electroencephalographyapparatus. 5-6. (canceled)
 7. The system of claim 1, wherein themonitoring apparatus comprises electromyography apparatus. 8-9.(canceled)
 10. The system of claim 1, wherein the monitoring apparatuscomprises electrooculography apparatus. 11-12. (canceled)
 13. The systemof claim 1, wherein system further comprises a self-contained patch andadhesive to attach the self-contained patch to the subject, wherein themonitoring apparatus, the auditory stimulation apparatus, and thecontroller are located on the self-contained patch.
 14. The system ofclaim 1, wherein the auditory stimulation apparatus comprises: memoryfor storing one or more selected auditory stimulations; and one or moreoutput devices, wherein the one or more output devices deliver the oneor more selected auditory stimulations.
 15. The system of claim 1,wherein the system further comprises a configuration apparatus toconfigure the system, wherein the configuration apparatus comprises:processing apparatus; a first input interface coupled to the processingapparatus to receive input from the subject; and an input/outputinterface coupled to the processing apparatus to transmit data to thecontroller of the stimulation system. 16-20. (canceled)
 21. A method ofstimulating a subject's brain, the method comprising: providing auditorystimulation apparatus for delivering a plurality of different auditorystimulations to a subject; providing monitoring apparatus to monitor thestate of the subject; positioning the auditory stimulation apparatuswhere the subject can hear the auditory stimulations; deliveringselected auditory stimulations from the plurality auditory stimulationsfrom the auditory stimulation apparatus to the subject during one ormore first periods when the subject is awake; and delivering theselected auditory stimulations from the plurality of auditorystimulations from the auditory stimulation apparatus to the subjectduring one or more second periods when the subject is asleep.
 22. Themethod of claim 21, wherein each first period of the one or more firstperiods has a finite duration during which the subject is learning aspecific task, and wherein each first period of the one or more firstperiods corresponds to a different specific task.
 23. The method ofclaim 21, wherein a different selected auditory stimulation of theplurality of different auditory stimulations is delivered to the subjectduring each first period of the one or more first periods, and furtherwherein each different selected auditory stimulation that was deliveredto the subject during each first period of the one or more first periodsis delivered to the subject during each second period of the one or moresecond periods.
 24. The method of claim 21, wherein the monitoringapparatus comprises electroencephalography apparatus to measureelectrical activity of the subject's brain.
 25. The method of claim 24,wherein electrical activity of the subject's brain indicative ofsawtooth waveforms before rapid eye movement occurs during each of theone or more second periods.
 26. (canceled)
 27. The method of claim 24further comprising: selecting each second period of the one or moresecond periods to correspond to a period when the electrical activity ofthe subject's brain is undergoing sawtooth waveforms before rapid eyemovement. 28-30. (canceled)
 31. The method of claim 24, whereinelectrical activity in the subject's brain indicative of slow wave sleepoccurs during each second period of the one or more second periods. 32.(canceled)
 33. The method of claim 24 further comprising: selecting eachsecond period of the one or more second periods to correspond to whenthe electrical activity of the subject's brain is undergoing slow wavesleep.
 34. (canceled)
 35. The method of claim 24, wherein electricalactivity in the subject's brain indicative of an increase in slope ofthe waveform of the electrical activity occurs during each second periodof the one or more second periods.
 36. The method of claim 24, whereinelectrical activity in the subject's brain indicative of an impendingincrease in slope of the waveform of the electrical activity occursduring each second period of the one or more second periods.
 37. Themethod of claim 24, wherein electrical activity in the subject's brainindicative of sleep spindles occurs during each second period of the oneor more second periods.
 38. (canceled)
 39. The method of claim 24further comprising: selecting each second period of the one or moresecond periods to correspond to a period when the electrical activity ofthe subject's brain is undergoing sleep spindles.
 40. (canceled)
 41. Themethod of claim 24, wherein electrical activity in the subject's brainindicative of stage II sleep immediately preceding rapid eye movementoccurs during each second period of the one or more second periods. 42.The method of claim 24 further comprising: selecting each second periodof the one or more second periods to correspond to a period when theelectrical activity of the subject's brain indicates that the subject isundergoing stage II sleep immediately preceding rapid eye movement. 43.(canceled)
 44. The method of claim 21, wherein rapid eye movement of thesubject occurs during each second period of the one or more secondperiods.
 45. The method of claim 21 further comprising: selecting eachsecond period of the one or more second periods to correspond with rapideye movement of the subject. 46-154. (canceled)